Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000941 | SCV001158040 | pathogenic | Hereditary factor VIII deficiency disease | 2018-12-05 | criteria provided, single submitter | clinical testing | The F8 c.6622C>G; p.Gln2208Glu variant, also known as Q2189E, is reported in the literature in multiple individuals affected with mild to moderate hemophilia A (David 2006, Fernandez-Lopez 2005, Johnsen 2017, Markoff 2009). This variant is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamine at codon 2208 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other variants at this codon (c.6623A>G, p.Gln2208Arg; c.6623A>C, p.Gln2208Pro) have been reported in individuals with mild to moderate hemophilia A and are considered pathogenic (Casana 2008, Cid 2007, Fernandez-Lopez 2005, Markoff 2009). Based on available information, the p.Gln2208Glu variant is considered to be pathogenic. References: Casana P et al. Severe and moderate hemophilia A: identification of 38 new genetic alterations. Haematologica. 2008 Jul;93(7):1091-4. Cid AR et al. Treatment in a haemophiliac A patient with paroxysmal atrial fibrillation and ischemic heart disease. Haemophilia. 2007 Nov;13(6):760-2. David D et al. The spectrum of mutations and molecular pathogenesis of hemophilia A in 181 Portuguese patients. Haematologica. 2006 Jun;91(6):840-3. Fernandez-Lopez O et al. The spectrum of mutations in Southern Spanish patients with hemophilia A and identification of 28 novel mutations. Haematologica. 2005 May;90(5):707-10. Johnsen JM et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 2017 May 18;1(13):824-834. Markoff A et al. Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function. Haemophilia. 2009 Jul;15(4):932-41. |
| Fulgent Genetics, |
RCV002481798 | SCV002784716 | pathogenic | Hereditary factor VIII deficiency disease; Thrombophilia, X-linked, due to factor 8 defect | 2021-10-22 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV003480899 | SCV004225554 | likely pathogenic | not provided | 2022-12-13 | criteria provided, single submitter | clinical testing | PP3, PM1_supporting, PM5, PS4_moderate |